Precursor frequency of participating T cells

The precursor frequency of unprimed T cells responding to typical non-MHC antigens, e.g. viral or foreign protein antigens, is extremely low (=£1 in 10s). Responses to MHC alloantigens, by contrast, involve a very high proportion of T cells. Working with rat lymphocytes in the late 1960s, Wilson, Blyth and Nowell estimated that 2-3% of unprimed T cells responded to stimulator cells from an MHC-different rat strain. Subsequent studies of others with mice gave similar data.

In view of the extensive polymorphism of MHC molecules, it is probable that the vast majority of T cells have the potential to display alloreactivity for at least one of the many different MHC alloantigens expressed in the species as a whole. In support of this idea, many T cell clones with defined self MHC-restricted specificity (specificity for antigen com-

plexed to self MHC molecules) have been shown to display dual reactivity for particular MHC alloantigens. Since T cells recognize conventional (non-MHC) antigens and MHC alloantigens via the same antigen-specific a|3 T cell receptor (TCR), these two classes of antigens are presumed to express cross-reactive epitopes. Why T cells have such a high precursor frequency for MHC alloantigens, however, is still something of a mystery.

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